Indications for early aspirin use in acute ischemic stroke - A combined analysis of 40 000 randomized patients from the Chinese Acute Stroke Trial and the International Stroke Trial

Background and Purpose-Long-term daily aspirin is of benefit in the years a lter ischemic stroke, and 2 large randomized trials (the Chinese Acute Stro ke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 pati ents in each, have shown that starting daily aspirin promptly in patients w ith suspected acute ischemic stroke also reduces the immediate risk of furt her stroke or death in hospital and the overall risk of death or dependency . However, some uncertainty remains about the effects of early aspirin in p articular categories of patient with acute stroke. Methods-To assess the balance of benefits and risks of aspirin in particula r categories of patient with acute stroke leg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta- analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatm ent period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 38 subgroups. This represents 99% of the worldwide evidence from randomized trials. Results-There was a highly significant reduction of 7 per 1000 (SD Ii in re current ischemic stroke (320 [1.6%] aspirin versus 457 [2.3%] control, 2P<0 .000001) and a less clearly significant reduction of 4 (SD 2) per 1000 in d eath without further stroke (5.0% versus 5.4%, 2P=0.05). Against these bene fits, there was an increase of 2 (SD 1) per 1000 in hemorrhagic stroke or h emorrhagic transformation of the original infarct (1.0% versus 0.8%, 2P= 0. 07) and no apparent effect on further stroke of unknown cause (0.9% versus 0.9%). In total, therefore, there was a net decrease of 9 (SD 3) per 1000 i n the overall risk of further stroke or death in hospital (8.2% versus 9.1% , 2P=0.001). For the reduction of one third in recurrent ischemic stroke, s ubgroup-specific analyses found no significant heterogeneity of the proport ional benefit of aspirin (chi(18)(2)=20.9, NS), even though the overall tre atment effect (X-1(2)=24.8, 2P<0.000001) was sufficiently targe for such su bgroup analyses to be statistically informative. The absolute risk among co ntrol patients was similar in all 28 subgroups, so the absolute reduction o f approximate to 7 per 1000 in recurrent ischemic stroke does not differ su bstantially with respect to age, sex, level of consciousness, atrial fibril lation, CT findings, blood pressure, stroke subtype, or concomitant heparin use. There was no good evidence that the apparent decrease of approximate to 4 per 1000 in death without further stroke was reversed in any subgroup or that in any subgroup the increase in hemorrhagic stroke was much larger than the overall average of approximate to 2 per 1000. Finally, there was n o significant heterogeneity between the reductions in the composite outcome of any further stroke or death (chi(18)(2)=16.5. NS). Among the 9000 patie nts (22%) randomized without a prior CT scan, aspirin appeared to be of net benefit with no unusual excess of hemorrhagic stroker; moreover, even amon g the 800 (2%) who had inadvertently been randomized after a hemorrhagic st roke, there was no evidence of net hazard (further stroke or death. 63 aspi rin versus 67 control). Conclusions-Early aspirin is of benefit for a wide range of patients, and i ts prompt use should be routinely considered for all patients with suspecte d acute ischemic stroke, mainly to reduce the risk of early recurrence.